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Updated: Feb 21, 2026
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Assessment of hepatic metabolism-dependent nephrotoxicity on an organs-on-a-chip microdevice
Zhongyu Li1, Lei Jiang2, Yujuan Zhu3
1Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, China.
Abstract:
Drug-induced nephrotoxicity is one of the most frequent adverse events in pharmacotherapy. It has resulted in numerous clinical trial failures and high drug development costs. The predictive capabilities of existing in vitro models are limited by their inability to recapitulate the complex process of drug metabolism at the multi-organ level in vivo. We present a novel integrated liver-kidney chip that allows the evaluation of drug-induced nephrotoxicity following liver metabolism in vitro. The liver-kidney chip consists of two polydimethylsiloxane layers with compartmentalized micro-channels separated by a porous membrane. Hepatic and renal cells were co-cultured in separate micro-chambers on a single chip. Ifosfamide and verapamil were used as model drugs, and their metabolites produced by hepatic metabolism were identified using mass spectrometry, respectively. The metabolites triggered significantly distinct nephrotoxic effects as assessed by cell viability, lactate dehydrogenase leakage and permeability of renal cells. This in vitro liver-kidney model facilitates the characterization of drug metabolism in the liver as well as the assessment of subsequent nephrotoxicity in a single assay. Obviously, this multi-organ platform is simple and scalable, and maybe widely applicable to the evaluation of drug metabolism and safety during the early phases of drug development.
Insights
This study introduces a novel liver-kidney chip for evaluating drug-induced nephrotoxicity. This integrated model assesses drug metabolism and kidney toxicity in vitro, improving drug development safety.
Area of Science:
- Biotechnology
- Toxicology
- Pharmacology
Background:
- Drug-induced nephrotoxicity is a major challenge in pharmacotherapy, causing clinical trial failures and increasing drug development costs.
- Current in vitro models lack the ability to replicate in vivo multi-organ drug metabolism, limiting predictive accuracy.
- Evaluating drug metabolism and subsequent organ toxicity requires sophisticated, integrated models.
Purpose of the Study:
- To develop and validate a novel integrated liver-kidney chip for assessing drug-induced nephrotoxicity.
- To enable in vitro evaluation of drug metabolism in the liver and its subsequent impact on kidney toxicity within a single platform.
- To provide a scalable and efficient model for early-stage drug development safety assessment.
Main Methods:
- An integrated liver-kidney chip was designed using polydimethylsiloxane with compartmentalized micro-channels and a porous membrane.
- Hepatic and renal cells were co-cultured in separate micro-chambers on the chip.
- Model drugs (Ifosfamide, Verapamil) were metabolized by hepatic cells, and their metabolites' nephrotoxic effects on renal cells were assessed.
Main Results:
- Mass spectrometry identified metabolites produced by hepatic metabolism of the model drugs.
- These metabolites induced distinct nephrotoxic effects, including changes in cell viability, lactate dehydrogenase leakage, and renal cell permeability.
- The liver-kidney chip successfully demonstrated differential toxicity based on drug metabolism.
Conclusions:
- The developed in vitro liver-kidney chip model effectively characterizes drug metabolism and assesses subsequent nephrotoxicity in a single assay.
- This multi-organ platform offers a simple, scalable, and widely applicable solution for evaluating drug metabolism and safety in early drug development.
- The model enhances the predictive capability of in vitro systems for drug-induced nephrotoxicity.
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